Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) are the causative agents of specific forms of leukemia/lymphomas in man. Much is known about the genetic structure and function of viral gene products and the role they play in viral replication and transformation in vitro. However, little is known about the processes which, over a relatively long latent period and in only a small proportion of individuals, result in leukemia. A complete understanding of the pathogenesis of the virus in man requires development of suitable experimental model systems. Here we design specific approaches to address the pathogenesis of HTLV in vivo. The Aims are: 1) to characterize HTLV-I- and II-infected cells in the peripheral blood of patients and asymptomatic carriers by FACS, in conjunction with RNA and DNA PCR; 2) to develop experimental animal model systems to investigate the pathogenesis of HTLV-I and -II utilizing the SCID mouse; and 3) to determine the role HTLV genes play in infectivity and transformation in vivo by mutagenesis and expression of genes from an infectious HTLV-II provirus clone.